Chapter 20 Carboxylic Acids Naming Carboxylic Acids Structure and ...
Chapter 20
Carboxylic Acids
Naming Carboxylic Acids Two systems have been adopted by IUPAC: 1) Carboxylic acids derived from open-chain alkanes are named by replacing the terminal –e of the alkane with –oic acid O CH3CH2
C
O OH
CH2CH3
HOC CH2 C CH2CH2
propanoic acid
H
CH3
O
C CH2 C OH H
3-ethyl-6-methyloctanedioic acid
2) Compounds that have a –COOH group bonded to a ring are named using the suffix –carboxylic acid COOH
COOH
Br
3-bromocyclohexanecarboxylic acid
1-cyclopentenecarboxylic acid
Structure and Properties of Carboxylic Acids - carboxyl carbon has sp2 hybridization; carboxyl group is therefore planar with C-C=O and O=C-O bond angles of approximately 120o O H H
C
C
O
H
H
- carboxylic acids are strongly associated by hydrogen bonds, most existing as cyclic dimers held together by two hydrogen bonds O H3C
H
O C
C O
H
CH3
O
1
Dissociation of Carboxylic Acids - carboxylic acids are acidic, with Ka ∼ 10-5 (pKa ∼ 5), and therefore react readily with a base such as NaOH to give a carboxylate salt O C
R
O
H2O
+ NaOH OH
C
R
+ H2O O Na+
metal-carboxylate salt
O
O C
R
Ka =
+ H2O
C
R
OH
[RCOO-][H3O+]
and
[RCOOH]
+ H3O+ O
pKa = -logKa
Relative Acidity of Carboxylic Acids - carboxylic acids are more acidic than alcohols by a factor of approximately 1011 O
CH3CH2OH
H3C
C
OH
pKa = 4.75
pKa = 16
HCl
pKa = -7
- Why? Acidity can be explained in terms of bonding CH3CH2OH + H2O
CH3CH2O
+ H3O+
not stabilized
O
O R
R
+ H2O
C O
O
C
R
C
O
H
O
stabilized by resonance
Substituent Effects on Acidity - acidity of carboxylic acids varies greatly according to the nature of the substituent attached to the carboxyl group - generally, any factor that stabilizes the carboxylate group relative to the undissociated acid will drive the equilibrium toward increased dissociation and result in increased acidity O
O
EWG
C
O
stabilizes carboxylate and strengthens acid
EDG
C
O
destabilizes carboxylate and weakens acid
- electron-withdrawing groups and electron-donating groups stabilize and destabilize carboxylate ions, respectively
2
Relative Strengths of Acetic Acid and Chloro- Derivatives
Substituent Effects in Substituted Benzoic Acids - electron-withdrawing (deactivating) and electron-donating (activating) groups stabilize and destabilize carboxylates O
O
O
C
C
C
OH
OH
OH
CH3O
O2N
p-methoxybenzoic acid (pKa = 4.46)
p-nitrobenzoic acid (pKa = 3.41)
benzoic acid (pKa = 4.19)
increasing acidity
Preparation of Carboxylic Acids 1) Oxidation of a substituted alkylbenzene using KMnO4 or Na2Cr2O7
O2N
CH3
O
KMnO4 H2O, 95oC
O2N
COH
p-nitrobenzoic acid (88%)
p-nitrotoluene
- occurs for primary and secondary alkyl groups (not tertiary) 2) Oxidative cleavage of an alkene with KMnO4 CH3(CH 2)7CH
CH(CH 2)7COOH
oleic acid
KMnO4 H3O+
CH 3(CH 2)7COOH nonanoic acid
+
HOOC(CH 2)7COOH nonanedioic acid
- alkene must have at least one vinylic hydrogen
3
3) Oxidation of a primary alcohol or an aldehyde O KMnO4
CH3(CH2)8CH2OH
CH3(CH2)8
H3O+
1-decanol
C
OH
decanoic acid (93%)
O
O
Ag2O
CH
CH3CH2CH2CH2CH2
COH
CH3CH2CH2CH2CH2
NH4OH
hexanal
hexanoic acid (85%)
- primary alcohols are oxidized with CrO3 in aqueous acid, aldehydes are oxidized with either acidic CrO3 or Tollen’s reagent
4) Hydrolysis of nitriles using strong, hot aqueous acid or base O
RCH2Br
NaCN
RCH2C
(SN2)
H3O+
N
RCH2 COH
- excellent two-step process for the preparation of carboxylic acids from primary halides
1) NaCN
O
CHCH 3 Br
O
2) -OH/H2O 3) H3
O
O+
CH COH CH 3
fenoprofen
- product has one more carbon than the starting alkyl halide
5) Carboxylation (or carbonation) of Grignard reagents MgBr
Br H3C
CH3
H3C
Mg
COOH CH3
ether
1) CO2, ether 2) H3
H3C
CH3
O+
CH3
CH3
CH3
1-bromo-2,4,6-trimethylbenzene
2,4,6-trimethylbezoic acid (87%)
- reaction is limited to alkyl halides that can form Grignard reagents (i.e. reactants with specific functional groups)
R:- +MgBr + O
O C
O R
C
O
H3O+
O
+MgBr
R
C
OH
4
General Reactions of Carboxylic Acids
Reduction of Carboxylic Acids - carboxylic acids can be reduced using two approaches: 1) Using LiAlH4 to give primary alcohols O CH3(CH2)7CH
CH (CH2)7 COH
1) LiAlH4, THF 2) H3O+
CH3(CH2)7CH
CH (CH2)7CH2OH
cis-9-octadecen-1-ol (87%)
oleic acid
- reaction usually requires harsh conditions (i.e. heating)
2) Using borane (BH3) to give primary alcohols O CH 2 COH
CH 2CH 2OH
1) BH3, THF 2) H3O+
O2N
p-nitrophenylacetic acid
O2N
2-(p-nitrophenyl)ethanol (94%)
- reaction is usually performed under mild conditions and can be used to selectively reduce carboxylic acid functionality
5
Spectroscopy of Carboxylic Acids Infrared Spectroscopy - two characteristic IR absorptions: 1) O-H gives broad band in the range 2500 - 330 cm-1 2) C=O gives band in the range 1710 - 1760 cm-1 - position depends on whether the acid exists as a monomer or hydrogen-bonded dimer O H3C
O
C O
H
monomer
H3C
H
O C
C O
H
CH3
O
hydrogen-bonded dimer
Infrared Spectrum of Butanoic Acid
NMR Spectroscopy - acidic -COOH proton absorbs as a singlet near 12 δ - carboxyl carbon atoms absorb in the range 165-185 δ - aromatic/saturated near 165 δ, aliphatic near 185 δ
6
1H
NMR Spectrum of Phenylacetic Acid
7
Carboxylic Acids
Naming Carboxylic Acids Two systems have been adopted by IUPAC: 1) Carboxylic acids derived from open-chain alkanes are named by replacing the terminal –e of the alkane with –oic acid O CH3CH2
C
O OH
CH2CH3
HOC CH2 C CH2CH2
propanoic acid
H
CH3
O
C CH2 C OH H
3-ethyl-6-methyloctanedioic acid
2) Compounds that have a –COOH group bonded to a ring are named using the suffix –carboxylic acid COOH
COOH
Br
3-bromocyclohexanecarboxylic acid
1-cyclopentenecarboxylic acid
Structure and Properties of Carboxylic Acids - carboxyl carbon has sp2 hybridization; carboxyl group is therefore planar with C-C=O and O=C-O bond angles of approximately 120o O H H
C
C
O
H
H
- carboxylic acids are strongly associated by hydrogen bonds, most existing as cyclic dimers held together by two hydrogen bonds O H3C
H
O C
C O
H
CH3
O
1
Dissociation of Carboxylic Acids - carboxylic acids are acidic, with Ka ∼ 10-5 (pKa ∼ 5), and therefore react readily with a base such as NaOH to give a carboxylate salt O C
R
O
H2O
+ NaOH OH
C
R
+ H2O O Na+
metal-carboxylate salt
O
O C
R
Ka =
+ H2O
C
R
OH
[RCOO-][H3O+]
and
[RCOOH]
+ H3O+ O
pKa = -logKa
Relative Acidity of Carboxylic Acids - carboxylic acids are more acidic than alcohols by a factor of approximately 1011 O
CH3CH2OH
H3C
C
OH
pKa = 4.75
pKa = 16
HCl
pKa = -7
- Why? Acidity can be explained in terms of bonding CH3CH2OH + H2O
CH3CH2O
+ H3O+
not stabilized
O
O R
R
+ H2O
C O
O
C
R
C
O
H
O
stabilized by resonance
Substituent Effects on Acidity - acidity of carboxylic acids varies greatly according to the nature of the substituent attached to the carboxyl group - generally, any factor that stabilizes the carboxylate group relative to the undissociated acid will drive the equilibrium toward increased dissociation and result in increased acidity O
O
EWG
C
O
stabilizes carboxylate and strengthens acid
EDG
C
O
destabilizes carboxylate and weakens acid
- electron-withdrawing groups and electron-donating groups stabilize and destabilize carboxylate ions, respectively
2
Relative Strengths of Acetic Acid and Chloro- Derivatives
Substituent Effects in Substituted Benzoic Acids - electron-withdrawing (deactivating) and electron-donating (activating) groups stabilize and destabilize carboxylates O
O
O
C
C
C
OH
OH
OH
CH3O
O2N
p-methoxybenzoic acid (pKa = 4.46)
p-nitrobenzoic acid (pKa = 3.41)
benzoic acid (pKa = 4.19)
increasing acidity
Preparation of Carboxylic Acids 1) Oxidation of a substituted alkylbenzene using KMnO4 or Na2Cr2O7
O2N
CH3
O
KMnO4 H2O, 95oC
O2N
COH
p-nitrobenzoic acid (88%)
p-nitrotoluene
- occurs for primary and secondary alkyl groups (not tertiary) 2) Oxidative cleavage of an alkene with KMnO4 CH3(CH 2)7CH
CH(CH 2)7COOH
oleic acid
KMnO4 H3O+
CH 3(CH 2)7COOH nonanoic acid
+
HOOC(CH 2)7COOH nonanedioic acid
- alkene must have at least one vinylic hydrogen
3
3) Oxidation of a primary alcohol or an aldehyde O KMnO4
CH3(CH2)8CH2OH
CH3(CH2)8
H3O+
1-decanol
C
OH
decanoic acid (93%)
O
O
Ag2O
CH
CH3CH2CH2CH2CH2
COH
CH3CH2CH2CH2CH2
NH4OH
hexanal
hexanoic acid (85%)
- primary alcohols are oxidized with CrO3 in aqueous acid, aldehydes are oxidized with either acidic CrO3 or Tollen’s reagent
4) Hydrolysis of nitriles using strong, hot aqueous acid or base O
RCH2Br
NaCN
RCH2C
(SN2)
H3O+
N
RCH2 COH
- excellent two-step process for the preparation of carboxylic acids from primary halides
1) NaCN
O
CHCH 3 Br
O
2) -OH/H2O 3) H3
O
O+
CH COH CH 3
fenoprofen
- product has one more carbon than the starting alkyl halide
5) Carboxylation (or carbonation) of Grignard reagents MgBr
Br H3C
CH3
H3C
Mg
COOH CH3
ether
1) CO2, ether 2) H3
H3C
CH3
O+
CH3
CH3
CH3
1-bromo-2,4,6-trimethylbenzene
2,4,6-trimethylbezoic acid (87%)
- reaction is limited to alkyl halides that can form Grignard reagents (i.e. reactants with specific functional groups)
R:- +MgBr + O
O C
O R
C
O
H3O+
O
+MgBr
R
C
OH
4
General Reactions of Carboxylic Acids
Reduction of Carboxylic Acids - carboxylic acids can be reduced using two approaches: 1) Using LiAlH4 to give primary alcohols O CH3(CH2)7CH
CH (CH2)7 COH
1) LiAlH4, THF 2) H3O+
CH3(CH2)7CH
CH (CH2)7CH2OH
cis-9-octadecen-1-ol (87%)
oleic acid
- reaction usually requires harsh conditions (i.e. heating)
2) Using borane (BH3) to give primary alcohols O CH 2 COH
CH 2CH 2OH
1) BH3, THF 2) H3O+
O2N
p-nitrophenylacetic acid
O2N
2-(p-nitrophenyl)ethanol (94%)
- reaction is usually performed under mild conditions and can be used to selectively reduce carboxylic acid functionality
5
Spectroscopy of Carboxylic Acids Infrared Spectroscopy - two characteristic IR absorptions: 1) O-H gives broad band in the range 2500 - 330 cm-1 2) C=O gives band in the range 1710 - 1760 cm-1 - position depends on whether the acid exists as a monomer or hydrogen-bonded dimer O H3C
O
C O
H
monomer
H3C
H
O C
C O
H
CH3
O
hydrogen-bonded dimer
Infrared Spectrum of Butanoic Acid
NMR Spectroscopy - acidic -COOH proton absorbs as a singlet near 12 δ - carboxyl carbon atoms absorb in the range 165-185 δ - aromatic/saturated near 165 δ, aliphatic near 185 δ
6
1H
NMR Spectrum of Phenylacetic Acid
7
